The pro-inflammatory cytokine tumor necrosis factor-alpha (TNF) contributes to injury-induced peripheral nerve pathology and to the development of neuropathic pain. Here, we investigated whether TNF protein is altered at the site of crush injury of rat sciatic nerve using enzyme-linked immunoassay (ELISA) and immunohistochemistry (IHC). TNF protein levels determined by ELISA were low in nerve homogenates from naive rats. After crush injury, local TNF increased rapidly with a two-fold increase on day 0.5. TNF content remained elevated on day 3 and returned to baseline levels again by day 14 after crush. IHC revealed prominent TNF-immunoreactivity in many epineurial macrophages on days 0.5 to 3 after crush injury. These data indicate that TNF protein is early and transiently upregulated at the site of peripheral nerve trauma.